tbuckley/cabot-search huggingface dataset:
Abstract 15349: Factors Associated With Progression of Latent Rheumatic Heart Disease
Authors: Andrea Z Beaton, Emmy Okello, Joselyn Rwebembera, Daniel Engelman, Jonathan Carapetis, ALYSSA DEWYER, Ndate Fall, Peter Lwabi, Mariana Mirabel, Ana O Mocumbi, miriam nakitto, Emma Ndagire, Maria D Nunes, Jafesi Pulle, Isaac Omara, Rachel Sarnacki, Amy Scheel, Nigel Wilson, Meghan Zimmerman, Liesl Zuhlke, Ganesan Karthikeyan, Craig A Sable, Anneke Grobler, Andrew Steer
Journal: Circulation (2022)

Introduction: Secondary antibiotic prophylaxis improves outcomes for children diagnosed with latent rheumatic heart disease (RHD). However, many children with latent RHD show improvement without prescription of prophylaxis. The objective of this study was to determine if specific sociodemographic or echocardiographic features are associated with progression of latent RHD. Methods: This is a retrospective analysis of the GOAL Trial, a randomized controlled trial of secondary antibiotic prophylaxis in children with latent RHD conducted in Uganda. Sociodemographic and echocardiographic variables were collected at trial entry. Progression was defined by a change in echocardiographic category according to the World Heart Federation Criteria (WHF; normal, borderline RHD, mild definite RHD, moderate/severe RHD), determined by consensus of a blinded 4-member adjudication panel. The association of risk factors with progression were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models adjusted for the randomized treatment arm and the stratification variable (definite/borderline RHD). Results: Outcomes for the 799 children who completed the GOAL Trial were included in this analysis. Female sex (OR 2.6, 95% CI 1.19-5.68, p=0.016) and poorer socioeconomic conditions (WAMI Index 0-1 with 1 being the least deprived, OR 0.48 for every 0.10-point increase) were associated with progression. There was no difference in risk of progression or regression between those with borderline RHD or mild definite RHD. Conclusions: Females and those living in less advantaged conditions were more likely to show progression of latent RHD. The strength of these associations was relatively low and does not warrant restricting prophylaxis to subgroups based on risk factors. The lack of difference in progression risk between those with borderline and those with definite RHD may impact revisions of the World Heart Federation Criteria for latent RHD diagnosis and calls into question the use of the term ‘borderline RHD’.
Abstract 15392: Radiation-Induced Coronary Microvascular Leakage is Mediated by Loss of Endothelial Tight Junction Protein Claudin-1
Authors: Sarmila Nepali, Shirley Xu, Swati D Sonkawade, Umesh C Sharma, Saraswati Pokharel
Journal: Circulation (2022)

Background: Ionizing radiation (IR) exposure to the heart during cancer therapy induces coronary microvascular leakage. Increased microvascular porosity allows inflammatory cell extravasation into the perivascular and myocardial interstitial space leading to fibrotic end organ damage. Hypothesis: Radiation-induced coronary microvascular leakage is mediated by a loss of a constitutively expressed tight-junction protein, claudin-1 (cldn1). Methods: We studied the function of cldn1 in human coronary vascular endothelial cells (HMVECs) and in mice using oligonucleotide-based cldn1 gene deletion. For the gain of function, we developed vascular-specific (VE-cadherin promotor-linked) claudin-1 overexpressing transgenic (TG) mice. We studied the effect of IR in cldn1 loss and gain of function models. Capillary permeability was assessed by FITC-dextran permeability and Evans blue dye injection, in vitro and in vivo, respectively . The extent of end-organ damage was examined by analyzing myocardial and perivascular fibrosis. Results: In HMVECs, cldn1 gene silencing (control, 1.0±0.34; siRNA, 0.026±0.03; p&lt;0.001) led to increased permeability (control, 1.0±0.01, siRNA, 1.3±0.01; p&lt;001). In mice, genetically engineered anti-cldn1 siRNA administration knocked down myocardial cldn1 expression (control, 1.0±0.18; siRNA, 0.51±0.11; p=0.04). Functionally, cldn1 knockdown led to increased microvascular extravasation (control, 1.0±0.23, cldn1-siRNA 0.38±0.27 p=0.002). Cardiac morphometry in these mice showed myocardial fibrosis (control, 1.0±0.19; siRNA, 1.29±0.35; p=0.048). Cardiac irradiation significantly decreased myocardial cldn1 (control 1.0±0.27, IR 0.45±0.31; p=0.001) and dye leakage (control 1.0±0.18, IR 1.28±0.22; p=0.007). Conversely, endothelium-targeted cldn1 overexpression in mice prevented abnormal microvasculature permeability (WT 1.0±0.23, TG 0.38±0.27 p=0.002) and conferred protection from IR-induced fibroinflammatory changes. Conclusions: Our study shows that cldn1 is crucial for maintaining coronary microvascular permeability. Prevention of cldn1 degradation or cldn1 reconstitution using novel pharmacotherapeutic approaches can prevent cardiac end-organ damage induced by cardiac IR.
Abstract 15300: Tirzepatide vs. Semaglutide for Weight Loss in Patients With Type 2 Diabetes Mellitus - A Value for Money Analysis
Authors: Joseph Azuri, Ariel Hammerman, Enis Aboalhasan, Ben Sluckis, Ronen Arbel
Journal: Circulation (2022)

Introduction: Higher doses of the glucagon-like peptide-1 agonist (GLP-1RA) semaglutide and, more recently, the GIP and GLP-1RA tirzepatide demonstrated a significant reduction in body weight in patients with Type 2 Diabetes Mellitus (T2DM). However, their comparative value for money for this indication is unclear. Hypothesis: Tirzepatide provides better value for money than semaglutide in facilitating weight loss. Methods: We calculated the cost needed to treat (CNT) to achieve a one percent reduction in body weight using high-dose tirzepatide (15mg) versus semaglutide (2.4mg). The body weight reductions were extracted from published results of SURMOUNT-1 and STEP 1 trials, respectively. We performed a scenario analysis to mitigate the primary differences between the two studies' populations (Table 1). Drug costs were based on US GoodRx prices as of June 2022. Results: Using tirzepatide resulted in weight loss of 17.8% (95% CI: 16.3%-19.3%) compared to 12.4% (95% CI: 11.5%-13.4%) for semaglutide. The total annual cost of therapy with tirzepatide was estimated at $17,554 compared with $22,899 for semaglutide. Accordingly, the CNT per one percent of body weight reduction with tirzepatide is estimated at $987 (95% CI:$910-$1,077) compared to $1,847 (95% CI: $1,708-$1,991) with semaglutide. Scenario analysis confirmed these findings. Conclusions: Tirzepatide provides better value for money than semaglutide for weight reduction at high doses.
Abstract 15101: Return-to-Work for Patients in High-Risk Professions Diagnosed With a Sudden Death-Predisposing Genetic Heart Disease
Authors: Veda K Kulkarni, Kathryn E Tobert, Johan M Bos, Clayton T Cowl, Ciorsti MacIntyre, John R Giudicessi, Michael J Ackerman
Journal: Circulation (2022)

Introduction: Sudden cardiac arrest (SCA) and death (SCD) are the most serious sequelae of many genetic heart diseases (GHDs). Increased awareness of this has led to increased detection in employment screenings. For patients in high-risk jobs, premature and potentially unnecessary termination from their profession, rather than “Return-to-Work (RTW),” has become an undesired consequence of this awareness. The objective of this study is to evaluate the outcomes of patients with GHDs in high-risk professions who were allowed to RTW. Methods: We performed a retrospective review of 3,641 working-age patients referred for evaluation of a potential GHD between 6/2000-12/2021 to identify those either in or being recruited into a high-risk profession. A profession was defined as “high-risk” if it is safety-sensitive or required regular medical evaluations. Charts were reviewed for medical history, RTW decision making, and breakthrough cardiac events (BCEs). Results: Overall, 33 patients [(0.9%); 3 females (9%); mean age at diagnosis 25 ± 15 years] had been either put on hold from their high-risk job (n = 15; 45%) or disqualified as a recruit (18; 55%) prior to our evaluation due to their GHD diagnosis. This included 15 military, 10 pilots, 6 law enforcement and first responders, and 2 commercial driver license professionals and recruits. Most patients were diagnosed with Long QT syndrome (n = 23; 70%). After treatment initiation, 14 (93%) professionals and 16 (89%) recruits received physician RTW approval while 3 (9%) patients did not receive RTW approval due to disease severity and/or unwillingness to initiate treatment. Of the remaining 14 professionals that received physician RTW approval, 4 (29%) were not allowed to return to their jobs, while 14/16 recruits (88%) were not permitted to start their career. None of the RTW-approved patients had a BCE after evaluation (160.7 follow-up years). Conclusions: Patients with GHDs in high-risk professions are often terminated due to perceived SCA/SCD risk. However, within our small cohort, the risk of BCEs in optimally treated patients was low. This data suggests that the certification process of individuals in these high-risk and safety-sensitive occupations should be further examined and potentially modified.
Abstract 15361: Rurality and Characteristics of Participants With Heart Failure in the Reasons for Geographic and Racial Differences in Stroke (Regards) Study
Authors: Stephen Clarkson, Todd Brown, Brittain F Heindl, Andrea Cherrington, Emily B Levitan, Elizabeth A Jackson, Aowen Zhu
Journal: Circulation (2022)

Introduction: Individuals living with heart failure (HF) in rural settings have higher age-adjusted mortality than urban dwelling individuals. Thus, we sought to examine sociodemographic and clinical differences between rural and urban populations with HF to better understand this disparity. Methods: We examined participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) population-based cohort who completed a computer-assisted telephone interview (CATI) 10-years following initial recruitment, and who either self-reported a history of HF or had an adjudicated HF hospitalization prior to the CATI. Rural and urban designations utilized a dichotomized adaption of the Rural Urban Commuting Area. We compared sociodemographic and clinical characteristics between rural/urban participants. Logistic regression was used to examine the association between depression and health literacy with urban dwelling. Results: A total of 1002 participants had self reported HF or an adjudicated HF hospitalization during approximately 10 years of follow-up, of which 195 (19%) were classified as rural. Rural dwelling participants with HF were younger (73.5 vs 75.4 years; p=0.004) and more likely to live in the stroke belt (45% vs 33%; p&lt;0.001), earn &lt;$20,000/year (27% vs 20%; p=0.030), experience depressive symptoms (52% vs 45%; p=0.05), and have low health literacy (24% vs 16%; p=0.02). Rural dwelling was associated with higher odds of low health literacy (aOR 1.79, CI 1.07-3.01; p=0.017) and depressive symptoms (aOR 1.13, CI 0.78-1.63; p=0.52). Conclusions: Rural dwelling participants with HF have a lower income and education than urban dwellers. Living in a rural setting was associated with a higher odds of having low health literacy, and half of rural dwelling participants with HF experience depressive symptoms. Addressing these factors may reduce rural/urban disparities in HF outcomes.
Abstract 14522: Infective Mitral Valve Endocarditis in an Immunocompetent Patient Caused by Lactobacillus Species Transmitted by Intranasal Cocaine Use
Authors: Amie M Kolimas, Muhammad Ajmal, Danielle D Avila, Rajesh Kotagiri, Toshinobu Kazui, Kevin J Moynahan, Michel T Corban
Journal: Circulation (2022)

A 59-year-old male with controlled DM2, HTN, tobacco abuse, and remote MSSA bacteremia secondary to longstanding intranasal cocaine use (never IV drug user) presented to the ER with acute onset of left leg pain. He was in extreme distress and examination showed a cold left leg with absent extremity pulses. Cardiac assessment was notable for an apical systolic murmur. Magnetic resonance angiography (MRA) of the leg revealed a thrombotic occlusion of the left common femoral artery extending into the popliteal artery prompting emergent successful femoral artery thrombectomy and compartment fasciotomy. An intraoperative TEE revealed mobile echodensities on the anterior and posterior MV leaflets with severe eccentric mitral regurgitation (MR) [Figure1]. Blood and thrombectomy debris cultures yielded Lactobacillus acidophilus vs. gasseri species. Further workup showed multiple small embolic infarcts on MRA head and chronic sinusitis on CT sinuses, while CT chest, abdomen and pelvis were unremarkable. He received IV ampicillin for 1 week with bacterial clearance, followed by bioprosthetic mitral valve replacement. Gram stain of the mitral valve revealed gram positive rods, cultures grew Lactobacillus species, and histopathology confirmed the presence of infective endocarditis. The patient completed 7 weeks of penicillin G intravenously with clinical recovery. Lactobacillus acidophilus and gasseri are normal flora of the human oral cavity, gastrointestinal and genitourinary tracts. Lactobacillus endocarditis is rare and has been identified in only 0.05-0.4% of endocarditis cases. Infections primarily affect the immunocompromised, but to the best of our knowledge this is the first case of Lactobacillus mitral valve endocarditis presenting with concomitant acute limb ischemia with infected thromboembolic debris in an immunocompetent individual with the suspected inciting event being intranasal cocaine use causing trauma to the nasal vasculature.
Abstract 15350: In-Hospital Outcomes of Transcatheter Aortic Valve Implantation in Patients With Peripheral Arterial Disease: Insights From the Nationwide Readmissions Database
Authors: Waqas Ullah, Muhammad Khawar Sana, Danish Iltaf Satti, Matthew DiMeglio, Aditya Munshi
Journal: Circulation (2022)

Introduction: Peripheral arterial disease (PAD) is associated with higher inpatient mortality among patients undergoing endovascular procedures. There is a paucity of data on the impact of PAD on clinical outcomes among patients undergoing transcatheter aortic valve implantation (TAVI). HypothesisPAD does not alter the clinical outcomes among patients undergoing TAVI. Methods: The National Readmission Database (NRD) from 2015-2019 was utilized to select patients with PAD undergoing TAVI. The adjusted odds ratio (OR) of net adverse cardiovascular events (NACE), its components (mortality, stroke), and major post-procedure complications were compared using a propensity-score-matched (PSM) analysis. Results: Using PSM, a total of 14,925 TAVI patients, 7,386 with PAD and 7,539 with no PAD were selected. At index admission, patients with PAD had significantly higher odds of NACE (5.10% vs 3.30% OR 1.60, 95% CI 1.36 to 1.88), and in-hospital mortality (2.10% vs. 0.50% OR 4.10, 95% CI 2.88-5.83) compared with patients without PAD. However, the odds of stroke (OR 1.00, 95% CI 0.74 to 1.35), major bleeding (OR 1.15, 95% CI 0.91-1.45), acute kidney injury (OR 0.98, 95% CI 0.90-1.08), cardiac tamponade (OR 0.88, 95% CI 0.59-1.32), valvular complications (OR 1.15, 95% CI 0.78-1.69), and cardiogenic shock (OR 1.62, 95% CI 0.97-2.70) were not significantly different between the two groups. Contrary to the index admission, there was no significant difference in the 30-day outcomes of patients with PAD and without PAD undergoing TAVI. Conclusion: TAVI in patients with PAD might be associated with a higher risk of NACE, and in-hospital mortality during the hospitalization of the index procedure. However, these complications attenuated at a follow-up of 30-days. The risk of other post-procedure complications remained similar between the two groups.
Abstract 15218: Hereditary Transthyretin Cardiac Amyloidosis in a Patient at High Risk for Plasma Cell Dyscrasias: A Complex Diagnostic Work-Up
Authors: Avery E Calhoun, Franck Azobou Tonleu, Matthew T Brown, Modele O Ogunniyi
Journal: Circulation (2022)

Background: Cardiac amyloidosis (CA) is most commonly caused by the infiltration of misfolded amyloid transthyretin (ATTR) or light chain (AL) molecules in the myocardium. The workup for CA requires serum assessment to exclude the rapidly progressive AL subtype before imaging to assess the more common and indolent ATTR form. The diagnostic algorithm has the potential to become complex as in this case about a woman with Sjogren’s syndrome which predisposes to plasma cell dyscrasias. Case: A 68-year-old female with congenital long QT syndrome requiring implantable cardioverter-defibrillator (ICD), bilateral carpal tunnel, and recent diagnosis of Sjogren’s syndrome was found to have new systolic heart failure during workup for interstitial lung disease. Labs revealed pancytopenia, abnormal kappa/lambda ratio (2.25), and polyclonal gammopathy on immunofixation. Echocardiogram showed moderately reduced systolic function with an ejection fraction of 35-40% and moderate concentric left ventricular hypertrophy. Decision-making: Cardiology obtained cardiac magnetic resonance imaging (CMR) that returned indeterminate due to ICD artifact. Hematology performed a bone marrow biopsy that was negative for plasma cell dyscrasia, though stained positive for amyloid on congo red with mass spectrometry revealing the valine 142 isoleucine (Val142Ile) amino acid substitution consistent with hereditary ATTR-CA. To definitively assess for endomyocardial ATTR involvement the patient was sent for cardiac scintigraphy using 99mTc-labeled pyrophosphate which returned negative with a cardiac to contralateral lung uptake ratio of 1.001 and visual grade of 0. With suspicion still high, an endomyocardial biopsy was pursued and stained positive for congo red with mass spectrometry confirming hereditary Val142Ile ATTR-CA, allowing for tafamidis initiation. Conclusion: We present a complex diagnostic case of ATTR amyloid in a patient who is at high risk for plasma cell dyscrasias with an abnormal kappa/lambda ratio, non-diagnostic CMR, and negative nuclear scan. Despite significant advances in imaging techniques allowing for less invasive diagnostics, this case highlights the role of endomyocardial biopsy in complicated cases.
Abstract 14424: Comparative Evaluation of Various Risk Scores in Non-ST-Segment Elevation Myocardial Infarction
Authors: Shekhar Kunal, Vijay Pathak, Pooja Pathak
Journal: Circulation (2022)

Introduction: Risk stratification is an integral component of the management strategy in patients with non-ST-elevation myocardial infarction (NSTEMI). Multiple risk scores have been proposed however, these have not been validated in developing countries such as India. Hypothesis: This study aims to determine the various prognostic factors in patients with NSTEMI as well as to compare and validate the performance of different risk stratification scores in these subjects. Methods: This was a single center prospective observational study wherein diagnosed with NSTEMI were enrolled. A detailed clinical history including symptomatology, presence of risk factors and family history were recorded. In all enrolled patients based on the prospectively collected data, five risk scores i.e. TIMI, GRACE version 2.0, PURSUIT, HEART and CAMI-NSTEMI were computed. Outcome data in terms of both in-patient as well as at 14 days, six months and one year major adverse cardiovascular events (MACE) were obtained. Results: A total of 1102 patients were enrolled with a mean age of 59.6 ± 11.2 years. MACE occurred in 140/1102 subjects (12.7%) with mortality in 89 (8.1%) patients. Patients with MACE were elderly, had higher frequency of smoking, hypertension, diabetes and stroke. Multivariate logistic regression analysis revealed that angina in last 48 hours, diabetes, smoking, cardiac arrest on presentation and fragmented QRS on ECG were independent predictors of MACE. All risk scores were able to predict MACE events equally well however, for in-hospital MACE, TIMI risk score had the highest predictive ability. However, for 14-day, 6 month and one year MACE, GRACE scores had highest predictive ability. Conclusions: Our study showed that all risk scores had a good predictive ability for both short term as well as intermediate-term MACE events.
Abstract 14573: High Performance of Artificial Intelligence-Based Model for Scoring Breast Arterial Calcification on Mammograms
Authors: Nitesh Nerlekar, Vinay Goel, Chee Yeong, Ella Spear, William Cameron, Richard Mantey, Nora Belrose, Stephen Nicholls
Journal: Circulation (2022)

Purpose: Mammographically detected breast arterial calcification (BAC) has been reported as a surrogate marker for coronary vascular disease (CVD). BAC is often not reported, reducing the power of this risk marker. Here we assess a deep-learning algorithm for BAC quantification, and in cases where the software identified BAC but the readers did not, assess correlation with clinical CVD. Methods: Screening digital mammograms (n=285, 1232 images) were selected from a tertiary Australian hospital from a sample of patients who underwent CVD screening (137 confirmed CVD). Two readers identified binary presence/absence of BAC. A deep learning software (cmAngio™ , CureMetrix, USA) quantified BAC score (scale 0-100). Reader-software discordance was adjudicated by a third observer. Area under the curve (AUC) was used to assess performance with 95% confidence intervals (CI) presented. Interobserver agreement was assessed by Cohen’s kappa (k). Results: Interobserver agreement for visual BAC was good (k=0.78, CI:0.71-0.85, p&lt;0.01). BAC scores ranged from 0-100, with 12% scoring 0. The algorithm had high performance, AUC 0.92 (CI:0.88-0.96, p&lt;0.001) vs initial reader assessment, increasing to AUC 0.98 (CI:0.97-0.99, p&lt;0.001) after adjudicated assessment. At an empirical threshold of BAC score ≥5 to denote BAC presence, BAC prevalence was 38% (109/285) by software, and 31% (87/285) visually. In cases where only the software identified BAC (n=35), BAC scores were all &lt;25, with 37% (n=13) having confirmed CVD and 9% (n=3) myocardial infarction. Conclusion: cmAngio demonstrates excellent performance for detecting BAC on screening mammograms. Faint BAC may be missed by human readers, is better identified by the software, and in these cases there is a high rate of CVD suggesting use in a screening population may improve risk prediction for CVD.